Evaluation of 5‐cis‐Substituted Prolinamines as Ligands in Enantioselective, Copper‐Catalyzed Henry Reactions
Evaluation of 5‐cis‐Substituted Prolinamines as Ligands in Enantioselective, Copper‐Catalyzed Henry Reactions
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DOI：
10.1002/cctc.201600240
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发表时间：
2016-05
期刊：
影响因子：
4.5
通讯作者：
Johannes Kaldun;Felix Prause;Dagmar Scharnagel;Frederik Freitag;M. Breuning
中科院分区：
文献类型：
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作者：
Johannes Kaldun;Felix Prause;Dagmar Scharnagel;Frederik Freitag;M. Breuning
介绍了一种新的对映选择性亨利反应的催化体系的发展，该体系可以与多种醛进行99%的ee反应。对33种由Boc - 1 -焦谷氨酸甲酯制备的5 -顺式取代的脯氨酸胺进行了深入的结构选择性研究，发现5 -顺式位置上的芳香族或具有空间要求的脂肪取代基对于高水平的立体控制至关重要，而氮原子上较大的取代基会降低对映选择性和反应速率。主要催化剂的范围扩大到克级和非对映体Henry反应（高达84:16 dr， 99% ee）。在机理研究过程中，证明了在反应条件下生成的β -硝基醇的构型是稳定的。此外，通过竞争实验确定了部分脯氨酸胺改性催化剂的相对反应速率。
The development of a new catalytic system for enantioselective Henry reactions, which permits superb 99 % ee with a broad variety of aldehydes, is presented. In‐depth structure–selectivity investigations with 33 5‐cis‐substituted prolinamines, prepared from methyl Boc‐l‐pyroglutamate, revealed that an aromatic or sterically demanding aliphatic substituent in 5‐cis position is crucial for high levels of stereocontrol, while bulkier substituents at the nitrogen atoms diminish both, enantioselectivities and reaction rates. The scope of the prime catalyst was expanded to gram‐scale and diastereomeric Henry reactions (up to 84:16 dr, 99 % ee). In the course of mechanistic studies, it was proven that the resulting β‐nitro alcohols are configurationally stable under the reaction conditions. In addition, competition experiments were used to determine the relative reaction rates of some of the prolinamine‐modified catalysts.